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Double-Blind, Randomized, Placebo-Controlled Multi-Center Phase III Study Followed By Open-Label Phase on the Efficacy and Tolerability of Budesonide in Patients with Resistant Oral Chronic GVHD: Part 1 - Efficacy Analysis
Objectives: Chronic GVHD (cGVHD) affects multiple organs, including the oral mucosa. When oral cGVHD is resistant to systemic treatment or when the oral mucosa is the only site affected, topical treatment can be an ideal treatment approach. The objective of this study is to compare the efficacy and tolerability of budesonide versus placebo for the treatment of resistant oral cGVHD. Methods: This study was a double-blind, randomized, placebo-controlled multi-center adaptive phase III clinical trial (DBP) followed by an open-label phase (OLP). In the DBP patients were treated with budesonide 3 mg effervescent tablet (9 mg/day) or placebo for 3 months. In the OLP all patients were treated with budesonide 9 mg/day for an additional 9 months. This study will be reported in 2 parts. For this part, the primary efficacy variable was defined as the proportion of patients showing an objective response at the final/withdrawal visit using the NIH scale and WHO response criteria. Several secondary efficacy variables were also determined. Results: Due to the fact that the second interim analysis revealed significant benefits in the budesonide group compared to controls (p=0.0203) the study was terminated. The final analysis including overrun patients did not show significant differences between the groups. Exploratory analyses of secondary outcomes showed favorable results for budesonide during DBP. The time to first occurrence of an objective response was shorter in the Budesonide group than the Placebo group (p=0.0416). During the OLP the improvement in all NIH subscores (ulcer, erythema, lichenoid and mucocele) was greater in the Budesonide group compared to controls (p<0.006). The post hoc analysis also supports the effectiveness of budesonide treatment. Conclusions: The study suggests that budesonide is effective for the topical treatment of resistant oral cGVHD based on numerous secondary efficacy variables. The significantly improved GVHD scores have important clinical relevance and concur with the finding of the second part of this study, in which symptomatic relief was demonstrated.